title: Varicella-zoster virus glycoprotein I is essential for spread in dorsal root ganglia and facilitates axonal localization of structural virion components in neuronal cultures.
abstract: Neurons of the sensory ganglia are the major site of varicella-zoster virus (VZV) latency and may undergo productive infection during reactivation. Although the VZV glycoprotein E/glycoprotein I (gE/gI) complex is known to be critical for neurovirulence, few studies have assessed the roles of these proteins during infection of dorsal root ganglia (DRG) due to the high human specificity of the virus. Here, we show that the VZV glycoprotein I gene is an important neurotropic gene responsible for mediating the spread of virus in neuronal cultures and explanted DRG. Inoculation of differentiated SH-SY5Y neuronal cell cultures with a VZV gI gene deletion strain (VZV rOkaΔgI) showed a large reduction in the percentage of cells infected and significantly smaller plaque sizes in a comparison with cultures infected with the parental strain (VZV rOka). In contrast, VZV rOkaΔgI was not significantly attenuated in fibroblast cultures, demonstrating a cell type-specific role for VZV gI. Analysis of rOkaΔgI protein localization by immunofluorescent staining revealed aberrant localization of viral glycoprotein and capsid proteins, with little or no staining present in the axons of differentiated SH-SY5Y cells infected with rOkaΔgI, yet axonal vesicle trafficking was not impaired. Further studies utilizing explanted human DRG indicated that VZV gI is required for the spread of virus within DRG. These data demonstrate a role for VZV gI in the cell-to-cell spread of virus during productive replication in neuronal cells and a role in facilitating the access of virion components to axons.
authors.affiliation: Discipline of Infectious Diseases and Immunology, The University of Sydney, Sydney, Australia.
authors.forename: Jenna
authors.initials: J
authors.lastname: Christensen
authors.forename: Megan
authors.initials: M
authors.lastname: Steain
authors.forename: Barry
authors.initials: B
authors.lastname: Slobedman
authors.forename: Allison
authors.initials: A
authors.lastname: Abendroth
mesh_terms: D001369:Axons / Q000821:virology*; D002460:Cell Line; D005727:Ganglia, Spinal / Q000821:virology*; D006562:Herpes Zoster / Q000821:virology*; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000821:virology*; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus